Among ion channels, potassium ion (K+) channels are the most ubiquitous and diverse. They include three major structural classes—channels with six, four, or two transmembrane domains. The six transmembrane domain potassium channels are divided further into different families, such as Shaker-like, eag-like and Slo-like potassium channels. Recent identification of KvLQT1 established a new family of six-transmembrane potassium channels. Barhanin et al. (1996) Nature 384: 78–80; Sanguinetti et al. (1996) Nature 384: 80–83; Yang et al. (1997) Proc. Natl. Acad. Sci. USA 94: 4017–22; Wang et al. (1996) Nature Genetics 12: 17–23. Search of DNA and protein sequence databanks reveals additional potential members of KvLQT1-related channels in C. elegans as well as in the human. Wei et al. (1996), Neuropharmacology 35: 805–29; Yang et al. (1997) Proc. Natl. Acad. Sci. USA 94: 4017–2.
One or more types of K+ channels reside on cell membranes where they are remarkably selective for K+ over other ions. In excitable cells, K+ channels modulate action potential configuration. Efflux of potassium is the major mechanism for repolarization, maintenance, and hyperpolarization of resting membrane potential. Halliwell (1990) in Potassium channels-structures, classification, function and therapeutic potential (N. S. Cook, ed.); 348–381; Jan, L. Y. and Jan, Y. N. (1992), Ann. Rev. Physiol. 54: 537–55; Pongs (1992), Physiol. Rev. 72: S69–S88.
In neurons, K+ channels regulate neuronal excitability, action potential shape and firing pattern, and neurotransmitter release. These channels can be gated by various stimuli, such as intracellular second messengers, membrane potential, ions, and neurotransmitters. Hille (1992), Ionic channels of excitable membranes; Catterall (1995), Ann. Rev. Biochem. 64: 493–531. Neuronal K+ channels are critical to such neuronal functions as neurotransmission and neuroprotection, and they may affect perception, learning, behavior, and the like.
Recently, the nomenclature for KvLQT1 and the KvLQT1-related channels was changed. Biervert et al. (1998), Science 279:403–406. KvLQT1 was re-named KCNQ1, and the KvLQT1-related channels (KvLR1 and KvLR2) were re-named as KCNQ2 and KCNQ3, respectively. Therefore, throughout this specification, reference to KCNQ1 is equivalent to KvLQT1; reference to KCNQ2 is equivalent to KvLR1; and reference to KCNQ3 is equivalent to KvLR2.
Benign familial neonatal convulsions (“BFNC”), a class of idiopathic generalized epilepsy, is an autosomal-dominantly inherited disorder of newborns. BFNC has recently been linked to mutations in two putative K+ channel genes, KCNQ2 and KCNQ3. Biervert et al., supra; Charlier et al. (1998), Nature Genetics 18:53–55; Singh et al. (1998) Nature Genetics 18:25–29. Preliminary functional characterization of KCNQ2 confirmed that this gene encodes a voltage-activated K+ channel. Singh et al., supra.